Infection, inflammation, fever, and resumption of health (with or without antimicrobial treatment)--this is the common view of the pathological course of infectious diseases. However, it has become apparent over the years that the mechanisms of diseases associated with infectious pathogens, particularly chronic disorders, may be the end product of a multitude of pathogenesis pathways. Moreover, in many cases the infectious pathogens may vary, but the clinical consequences of the resulting inflammatory responses may lead to similar, if not identical, disease expression. Consider that infecting agents may produce chronic disease through a variety of mechanisms, besides by immediate, direct damage of infected cells. Pathogens may infect persistently--sometimes in apparent clinical silence--with evidence of disease arising many years later. Connection between the infection and the disease state may be abundantly apparent when a majority of infected individuals ultimately exhibit the diseases symptoms. However, when only a minority of those infected develop chronic disease symptoms the etiologic link between an infectious organism and the chronic disease symptoms may be harder to connect. Even when connections between persistent infection with an organism and a specific disease are firmly established confusion can arise when the disease association is restricted to only a few strains of a larger pathogen species. Sometimes an organism is difficult to recover or identify or is even not sought because an infectious etiology is not seriously considered. Further, in some cases even when the infection is transient and the organism is cleared, a chronic disease state can be left behind due to a variety of mechanisms, including autoimmunity due to immune mimicry. The value of the immune response in removing the infecting pathogen is clear; however, what is also clear is the delicate balance between effective and damaging--or immunopathogenic/immunological activity. With new diagnostic and investigative techniques available to identify previously unsuspected pathogens, we are poised scientifically to answer the diagnostic and mechanistic medical dilemmas that have been around for centuries surrounding the possibility of infectious causes of chronic diseases. However, it is important to develop a new and careful medico-research approach to this issue, to frame and ask the right questions, and to think creatively about how to answer these questions. It is also important to develop a sound experimental framework to approach this issue, combining the best of clinical medical approaches, clinical research studies, animal models, and basic research investigations. The American Academy of Microbiology plans to convene a colloquium on "Microbial Triggers of Chronic Illness" to address just these issues. The colloquium is scheduled for January 15-18, 2004 in Tucson, Arizona. A group of approximately 25 scientists, including the steering committee, will be invited to participate in this colloquium. [unreadable] [unreadable]